Inducible Bcl-2 gene RNA interference mediated by aptamer-integrated HDV ribozyme switch,Integrative Biology

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Inducible Bcl-2 gene RNA interference mediated by aptamer-integrated HDV ribozyme switch
Integrative Biology ( IF 1.5 ) Pub Date : 2017-05-26 , DOI: 10.1039/c7ib00029d
Yuanyuan Zhang _{1,

2,

3,

4,

5} , Jine Wang _{4,

5,

6,

7,

8} , Hui Cheng _{4,

5,

6,

7,

8} , Na Sun _{4,

5,

6,

7,

8} , Min Liu _{4,

5,

6,

7,

8} , Zhengyan Wu _{4,

7,

9,

10,

11} , Renjun Pei _{4,

5,

6,

7,

8}

Affiliation

The regulation of RNA interference (RNAi) could be a powerful method for the study of temporal and dose dependent effects of gene expression. In this study, we designed the hepatitis delta virus (HDV) ribozyme with an embedded theophylline aptamer as the sensor domain and the pri-miRNA of endogenous gene Bcl-2 as the effector domain to engineer an RNAi-regulatory device in MCF-7 cells. The system allowed us to control gene expression by adding theophylline into the culture media in a dose dependent fashion. This is the pioneering application of ribozyme switches to activate RNAi for modulating endogenous genes in mammalian cells. The platform sets the stage for investigations of other endogenous genes that regulate various biological functions such as differentiation, cell division or cell death, and provides a promising interface with other universal RNAi-based decision-making circuits that operate in mammalian cells. It can be used to study more genes associated with cancer and screen for potential drug targets for gene therapy.

中文翻译：

适体整合的HDV核酶开关介导的可诱导的Bcl-2基因RNA干扰

RNA干扰（RNAi）的调控可能是研究基因表达的时间和剂量依赖性效应的有力方法。在这项研究中，我们设计了带有嵌入式茶碱适体作为传感器结构域，内源基因Bcl-2的pri-miRNA作为效应结构域的肝炎三角洲病毒（HDV）核酶，以工程化MCF-7细胞中的RNAi调控装置。。该系统允许我们通过以剂量依赖性方式将茶碱添加到培养基中来控制基因表达。这是核酶开关激活RNAi调节哺乳动物细胞内源基因的开创性应用。该平台为研究调节各种生物学功能（例如分化，细胞分裂或细胞死亡）的其他内源基因奠定了基础。并与在哺乳动物细胞中运行的其他基于通用RNAi的决策电路提供了有希望的接口。它可以用于研究与癌症有关的更多基因，并筛选用于基因治疗的潜在药物靶标。

更新日期：2017-05-26

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